Is AR p.His415Arg (c.1244A>G) pathogenic?

AR p.His415Arg (c.1244A>G) is classified Uncertain significance in AR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-16). AlphaMissense: likely benign (0.1078); Very rare (popmax 0.000113%, nfe); Associated with male infertility.

What condition is associated with AR p.His415Arg (c.1244A>G)?

AR p.His415Arg (c.1244A>G) is associated with male infertility (ClinVar).

How common is AR p.His415Arg (c.1244A>G) in the general population?

AR p.His415Arg (c.1244A>G) is very rare (popmax 0.000113%, nfe) (gnomAD).

What do computational predictors say about AR p.His415Arg (c.1244A>G)?

AlphaMissense predicts likely benign (score 0.1078) — an in-silico prediction, not a clinical call.

AR p.His415Arg

c.1244A>G · rs1255992515 · VCV3061772

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1078 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000113%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

male infertility

Computational evidence

Protein change
AlphaMissense	0.1078	likely benign
REVEL	0.685	pathogenic-leaning
SaProt	LLR -5.26	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9	GERP 2.1, phastCons 1
Overall
CADD	18.67	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000113% European (non-Finnish) · 1/881,950 alleles

Overall 0.000899% 1/111,193 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: AR
Protein: p.His415Arg
Coding: c.1244A>G
MANE Select: NM_000044
dbSNP: rs1255992515
Type: single nucleotide variant
Location: chrX:67546390 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 415: the 'interaction with znf318' region; the 'modulating' region

Full AR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

male infertility — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AR p.His415Tyr Benign ★ same residue
AR p.Arg856His Pathogenic/Likely pathogenic ★★ same condition
AR p.Asn757Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
AR p.Tyr408Cys Uncertain significance ★★ ⚠ same condition
AR p.Arg618Trp Likely pathogenic ★ same condition
AR p.Arg787Gln Likely pathogenic ★ same condition
AR p.Asp829Val Pathogenic ★ same condition
AR p.Cys687Arg Pathogenic ★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ar-p-his415arg (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown